Comparing the effects of different acupoint-stimulating therapies in mitigating post-stroke spasticity and motor dysfunction in older stroke survivors: A network meta-analysis of randomized trials.

Acupoint-stimulating therapies have often been used to manage stroke-related spasticity and motor dysfunction. However, the effects of different acupoint-stimulating therapies in older stroke survivors have been unclear. This systematic review and network meta-analysis compared the effects of different acupoint-stimulating therapies in managing spasticity and motor dysfunction in older stroke survivors. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched 7 databases for studies published up to July 2023. Inclusion criteria were: (1) older adults with strokes; (2) treatments were acupoint-stimulating therapies; (3) a control group did not receive acupoint-stimulating therapy, or the study compared different acupoint-stimulating therapies; and (4) outcomes included spasticity and motor function. Methodological quality was assessed with Risk-of-bias tool for randomized trials version 2, while R and Metainsight were used to conduct the network meta-analysis. We analyzed 27 studies and the results showed that non-invasive electroacupuncture and warm acupuncture were more effective in reducing spasticity than conventional acupuncture (standardized mean difference and 95 % confidence intervals = 1.35/1.19 [0.57; 2.13/0.54; 1.83]) and invasive electroacupuncture (standardized mean difference and 95 % confidence intervals = 0.96/0.80 [0.12; 1.80/0.08; 1.51]). Conventional acupuncture and invasive electroacupuncture were effective in improving motor function (standardized mean difference and 95 % confidence intervals = 0.99/1.41 [0.42; 1.56/0.54; 2.28]). However, there was significant inconsistency for the effects of invasive electroacupuncture between studies. Our findings suggest that for older stroke survivors with spasticity, non-invasive electroacupuncture and warm acupuncture are appropriate, whereas conventional acupuncture is more appropriate for patients aiming for motor recovery. SYSTEMATIC REVIEW REGISTRATION: This study was registered in the PROSPERO database (CRD42023442202).

Effects of Different Mind-body Exercises in Managing Chronic Pain of Older Adults: A Network Meta-analysis of Randomized Trials.

INTRODUCTION: Mind-body exercises (MBEs) were shown to be effective in managing chronic pain among older adults in several recent studies. However, the differences in the effects of different MBEs remained unclear. OBJECTIVE: To compare the effects of different MBEs in managing chronic pain in older adults. METHODS: Eight databases were searched for studies published between 2012 and 2023, and 14 studies were included in this systematic review and network meta-analysis (NMA). The NMA was performed using R and Metainsight. RESULTS: Results showed that tai chi and yoga were effective in alleviating chronic pain, but their effects were not superior to traditional physical exercises and other MBEs. In addition, none of the MBEs were shown to be effective in mitigating chronic pain-related disabilities. CONCLUSION: Tai chi and yoga can be used for relieving chronic pain in older adults; however, MBE programs alone were not sufficient to mitigate chronic pain-related disabilities.

Swimming exercise attenuates mechanical hypersensitivity and mitigates peripheral nerve degeneration in rats with painful diabetic neuropathy (PDN).

BACKGROUND: This study aimed to assess the effectiveness of swimming exercise in alleviating mechanical hypersensitivity and peripheral nerve degeneration associated with a pre-clinical model of painful diabetic neuropathy (PDN). METHODS: This study is a pre-clinical study conducted using the streptozocin (STZ)-induced PDN rat model. Rats were randomly allocated to three groups: a vehicle group of non-diabetic rats (Vehicle, n = 9), a group of rats with PDN (PDN, n = 8), and a group of rats with PDN that performed a swimming exercise program (PDN-SW, n = 10). The swimming exercise program included daily 30-minute swimming exercise, 5 days per week for 4 weeks. Von Frey testing was used to monitor hindpaw mechanical sensitivity over 4 weeks. Assessment of cutaneous peripheral nerve fiber integrity was performed after the 4-week study period via immunohistochemistry for protein gene product 9.5-positive (PGP9.5+) intra-epidermal nerve fiber density (IENFD) in hind-paw skin biopsies by a blinded investigator. RESULTS: The results showed that swimming exercise mitigated but did not fully reverse mechanical hypersensitivity in rats with PDN. Immunohistochemical testing revealed that the rats in the PDN-SW group retained higher PGP9.5+ IENFD compared to the PDN group but did not reach normal levels of the Vehicle group. CONCLUSIONS: The results of this study indicate that swimming exercise can mitigate mechanical hypersensitivity and degeneration of peripheral nerve fibers in rats with experimental PDN.

Comparing Different Stretching Exercises on Pain, Stiffness, and Physical Function Disability in Older Adults With Knee Osteoarthritis.

OBJECTIVE: To assess and compare the effects of different stretching exercise programs on pain, stiffness, and physical function disability in older adults with knee osteoarthritis (KOA). DATA SOURCES: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline for network meta-analysis (NMA). Relevant randomized controlled trials were identified by searching 7 databases up to December 2022. STUDY SELECTION: Inclusion criteria included (1) older adults with KOA; (2) intervention included stretching exercises; (3) control groups received no stretching exercise; and (4) outcome measurements included pain, stiffness, or physical function disability. Methodological quality was assessed using the Cochrane risk-of-bias tool for randomized trials version 2. DATA EXTRACTION: NMA was performed using R and MetaInsight, with results presented as a standardized mean difference (SMD) with 95% confidence interval (CI). DATA SYNTHESIS: We examined 17 studies, and NMA results indicated that proprioceptive neuromuscular facilitation (PNF) stretching, mind-body exercises, and multi-component exercise programs were effective in mitigating pain in older adults with KOA (SMD=2.54 [95% CI: 1.23; 3.84], SMD=1.09 [95% CI: 0.27; 1.92], SMD=0.57 [95% CI: 0.06; 1.09]). Moreover, mind-body exercises and multi-component exercises were the most effective programs in reducing stiffness (SMD=1.31 [95% CI: 0.12; 2.51]) and physical function disability (SMD=1.67 [95% CI: 0.01; 3.33]) in older adults with KOA, respectively. CONCLUSION: Findings suggest that PNF stretching, mind-body exercises, and multi-component exercises can be incorporated into exercise programs to better mitigate pain, stiffness, and physical function disability in older adults with KOA.

Physical therapy for sleep apnea: a smartphone application for home-based physical therapy for patients with obstructive sleep apnea.

Purpose: In this study, we described "PT for Sleep Apnea", a smartphone application for home-based physical therapy of patients with Obstructive Sleep Apnea (OSA). Methods: The application was created in a joint program between the University of Medicine and Pharmacy at Ho Chi Minh City (UMP), Vietnam, and National Cheng Kung University (NCKU), Taiwan. Exercises maneuvers were derived from the exercise program previously published by the partner group at National Cheng Kung University. They included exercises for upper airway and respiratory muscle training and general endurance training. Results: The application provides video and in-text tutorials for users to follow at home and a schedule function to assist the user in organizing the training program, which may improve the efficacy of home-based physical therapy in patients with Obstructive Sleep Apnea. Conclusion: In the future, our group plans to conduct a user study and randomized-controlled trials to investigate whether our application can benefit patients with OSA.

Naphazoline and oxymetazoline are superior to epinephrine in enhancing the cutaneous analgesia of lidocaine in rats.

This study observed the cutaneous analgesic effect of adrenergic agonists when combined with lidocaine. We aimed at the usefulness of four adrenergic agonists and epinephrine as analgesics or as tools to prolong the effect of local anesthetics using a model of cutaneous trunci muscle reflex (pinprick pain) in rats. We showed that subcutaneous four adrenergic agonists and epinephrine, as well as the local anesthetic bupivacaine and lidocaine, developed a concentration-dependent cutaneous analgesia. The rank order of the efficacy of different compounds (ED50 ; median effective dose) was epinephrine [0.013 (0.012-0.014) µmol] > oxymetazoline [0.25 (0.22-0.28) µmol] > naphazoline [0.42 (0.34-0.53) µmol] = bupivacaine [0.43 (0.37-0.50) µmol] > xylometazoline [1.34 (1.25-1.45) µmol] > lidocaine [5.86 (5.11-6.72) µmol] > tetrahydrozoline [6.76 (6.21-7.36) µmol]. The duration of full recovery caused by tetrahydrozoline, oxymetazoline, or xylometazoline was greater (P < 0.01) than that induced via epinephrine, bupivacaine, lidocaine, or naphazoline at equianesthetic doses (ED25 , ED50 , and ED75 ). Co-administration of lidocaine (ED50 ) with four adrenergic agonists or epinephrine enhanced the cutaneous analgesic effect. We observed that four adrenergic agonists and epinephrine induce analgesia by themselves, and such an effect has a longer duration than local anesthetics. Co-administration of lidocaine with the adrenergic agonist enhances the analgesic effect, and the cutaneous analgesic effect of lidocaine plus naphazoline (or oxymetazoline) is greater than that of lidocaine plus epinephrine.

Cutaneous expression of growth-associated protein 43 is not a compelling marker for human nerve regeneration in carpal tunnel syndrome.

Growth-associated protein 43 (GAP-43) has long been used as a marker for nerve regeneration following nerve injury, with numerous in vitro and animal studies showing its upregulation in regenerating neurons. In humans, expression of GAP-43 has predominantly been examined in skin biopsies from patients with peripheral neuropathies; with several studies showing a reduction in GAP-43 immunoreactive cutaneous nerve fibres. However, it remains elusive whether cutaneous GAP-43 is a valid marker for human nerve regeneration. Here, we present a cohort of 22 patients with electrodiagnostically confirmed carpal tunnel syndrome (CTS), used as a model system for focal nerve injury and neural regeneration after decompression surgery. We evaluate GAP-43 immunoreactivity and RNA expression levels in finger skin biopsies taken before and 6 months after surgery, relative to healthy controls. We further classify patients as 'regenerators' or 'non-regenerators' based on post-surgical epidermal re-innervation. We demonstrate that patients with CTS have lower GAP-43 positive intra-epidermal nerve fibre density (IENFD) before surgery than healthy controls. However, this difference disappears when normalising for total IENFD. Of note, we found surgery did not change GAP-43 expression in IENF, with no differences both in patients who were classified as regenerators and non-regenerators. We also did not identify pre-post surgical differences in cutaneous GAP-43 gene expression or associations with regeneration. These findings suggest cutaneous GAP-43 may not be a compelling marker for nerve regeneration in humans.

Effects of Neural Mobilization on Sensory Dysfunction and Peripheral Nerve Degeneration in Rats With Painful Diabetic Neuropathy.

OBJECTIVE: This study aims to evaluate the effectiveness of neural mobilization (NM) in the management of sensory dysfunction and nerve degeneration related to experimental painful diabetic neuropathy (PDN). METHODS: This is a pre-clinical animal study performed in the streptozocin-induced diabetic rat model. Three groups were included: a treatment group of rats with PDN receiving NM under anesthesia (PDN-NM, n = 10), a sham treatment group of rats with PDN that received only anesthesia (PDN-Sham, n = 9), and a vehicle control group with nondiabetic animals (Vehicle, n = 10). Rats in the PDN-NM and PDN-Sham groups received 1 treatment session on days 10, 12, and 14 after streptozocin injection, with a 48-hour rest period between sessions. Behavioral tests were performed using von Frey and Plantar tests. Evaluation for peripheral nerve degeneration was performed through measuring protein gene product 9.5-positive intra-epidermal nerve fiber density in hind-paw skin biopsies. All measurements were performed by a blinded investigator. RESULTS: The behavioral tests showed that a single NM session could reduce hyperalgesia, which was maintained for 48 hours. The second treatment session further improved this treatment effect, and the third session maintained it. These results suggest that it requires multiple treatment sessions to produce and maintain hypoalgesic effects. Skin biopsy analysis showed that the protein gene product 9.5-positive intra-epidermal nerve fiber density was higher on the experimental side of the PDN-NM group compared with the PDN-Sham group, suggesting NM may mitigate the degeneration of peripheral nerves. CONCLUSION: This study demonstrated that NM may be an effective method to manage experimentally induced PDN, potentially through mitigation of nerve degeneration. Further studies are needed to develop standardized protocols for clinical use. IMPACT: These findings provide neurophysiological evidence for the use of NM in PDN and can form the basis for the development of physical therapy-based programs in clinics.

Intrathecal pramipexole and selegiline for sensory and motor block in rats.

BACKGROUND: The purpose of the study was to investigate spinal sensory and motor block by antiparkinsonian drugs (pramipexole and selegiline), and the combination of pramipexole and the local anesthetic lidocaine. METHODS: Using a technique of spinal blockade in rats, the effects of pramipexole, selegiline, and coadministration of pramipexole and lidocaine on spinal blockades of motor and sensory function were investigated. RESULTS: Under a concentration of 100 mM, pramipexole displayed more potent and had a longer duration of nociceptive, proprioceptive, and motor block than selegiline, whereas pramipexole and selegiline were less potent in comparison to lidocaine. Pramipexole produced spinal nociceptive, proprioceptive, and motor blocks in a dose-related manner. On the ED50 (50% effective dose) basis, the rank-order potency on nociceptive, proprioceptive, and motor block was pramipexole < lidocaine. The spinal block duration of pramipexole was greater than lidocaine at every equipotent dose tested (ED25, ED50, and ED75). Coadministration of lidocaine (ED50 or ED95) with pramipexole (4.5 µmol/kg) improved the effect (efficacy) and duration of the spinal block. CONCLUSIONS: Pramipexole and selegiline were less potent than lidocaine to block sensory and motor responses. The duration of the spinal anesthetic effect of pramipexole was longer than lidocaine. At a non-effective dose, pramipexole increased the duration of efficacy of lidocaine.

Concurrent validity of a low-cost and time-efficient clinical sensory test battery to evaluate somatosensory dysfunction.

BACKGROUND: This study describes a low-cost and time-efficient clinical sensory test (CST) battery and evaluates its concurrent validity as a screening tool to detect somatosensory dysfunction as determined using quantitative sensory testing (QST). METHOD: Three patient cohorts with carpal tunnel syndrome (CTS, n = 76), non-specific neck and arm pain (NSNAP, n = 40) and lumbar radicular pain/radiculopathy (LR, n = 26) were included. The CST consisted of 13 tests, each corresponding to a QST parameter and evaluating a broad spectrum of sensory functions using thermal (coins, ice cube, hot test tube) and mechanical (cotton wool, von Frey hairs, tuning fork, toothpicks, thumb and eraser pressure) detection and pain thresholds testing both loss and gain of function. Agreement rate, statistical significance and strength of correlation (phi coefficient) between CST and QST parameters were calculated. RESULTS: Several CST parameters (cold, warm and mechanical detection thresholds as well as cold and pressure pain thresholds) were significantly correlated with QST, with a majority demonstrating >60% agreement rates and moderate to relatively strong correlations. However, agreement varied among cohorts. Gain of function parameters showed stronger agreement in the CTS and LR cohorts, whereas loss of function parameters had better agreement in the NSNAP cohort. Other CST parameters (16 mN von Frey tests, vibration detection, heat and mechanical pain thresholds, wind-up ratio) did not significantly correlate with QST. CONCLUSION: Some of the tests in the CST could help detect somatosensory dysfunction as determined with QST. Parts of the CST could therefore be used as a low-cost screening tool in a clinical setting. SIGNIFICANCE: Quantitative sensory testing, albeit considered the gold standard to evaluate somatosensory dysfunction, requires expensive equipment, specialized examiner training and substantial time commitment which challenges its use in a clinical setting. Our study describes a CST as a low-cost and time-efficient alternative. Some of the CST tools (cold, warm, mechanical detection thresholds; pressure pain thresholds) significantly correlated with the respective QST parameters, suggesting that they may be useful in a clinical setting to detect sensory dysfunction.

Neural Mobilization Attenuates Mechanical Allodynia and Decreases Proinflammatory Cytokine Concentrations in Rats With Painful Diabetic Neuropathy.

Background: Painful diabetic neuropathy (PDN) is a common complication in patients with diabetes. It is related to ischemic nerve damage and the increase in the levels of proinflammatory mediators, such as tumor necrosis factor α (TNF-α) and interleukin 1ß (IL-1ß). Neural mobilization may have the potential to alleviate PDN, but it has not yet been tested. Also, the physiological mechanism of neural mobilization is unclear. Objective: The objective of this study was to investigate treatment effect and physiological mechanism of neural mobilization. Design: This was an experimental study using rats with streptozocin (or streptozotocin)-induced type 1 diabetes. Methods: Three groups were used in the study, the control group (vehicle), the diabetes group (PDN group), and the neural mobilization treatment group (PDN-NM group) (n = 6). Rats in the vehicle group were healthy rats. Rats in the PDN and PDN-NM groups were rats with diabetes. Rats in the PDN-NM group received treatment in the right sciatic nerve, whereas rats in the PDN group did not. Mechanical pain sensitivity and the levels of IL-1ß and TNF-α in the sciatic nerve branches and trunk, the L4 to L6 dorsal horn ganglion, and the spinal cord dorsal horn were measured. Results: Techanical allodynia was alleviated after treatment, but the effect was limited to the treatment side. The concentrations of proinflammatory cytokines were decreased in the nerves that received treatment compared with those on the other side, indicating that neural mobilization may reduce mechanical sensitivity by decreasing the concentrations of local sensitizing agents. Limitations: A limitation of this study was that no direct measurement of nerve blood flow was done. Conclusions: The results of this study showed that neural mobilization effectively alleviated mechanical allodynia in rats with PDN. The side that received treatment had lower concentrations of TNF-α and IL-1ß in the sciatic nerve branches and sciatic nerve trunk; this result may have been related to the alleviation of mechanical allodynia.